Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined the expression levels of the mdr1 and mdr3 multidrug-resistance genes (also known as PGY1 and PGY3, respectively) in peripheral blood cells from 69 adult patients with acute and chronic leukemias, using an RNase protection assay. Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven). Expression of mdr3 was only detected in samples from B-cell lymphocytic leukemias: CML, lymphoid blast crisis (one of one), B-cell ALL (two of two), B-CLL (17 of 17), B-PLL (seven of seven), and HCL (two of two). In vitro drug uptake studies by on-line flow cytometry showed that in leukemia cells expressing either mdr1 or mdr3, the steady-state accumulation of daunorubicin could be significantly increased by addition of cyclosporine and, to a lesser extent, by verapamil. Because cyclosporine and verapamil are known as inhibitors of the mdr1-encoded P-glycoprotein drug-efflux pump, and because the mdr1 and mdr3 genes are highly homologous, our data suggest that the mdr3 gene encodes a functional drug pump in B-cell lymphocytic leukemias. The results of this study may have implications for clinical therapy for acute or chronic leukemias expressing the mdr1 or mdr3 gene, in particular, treatment with combinations of cytotoxic drugs plus agents that reverse multidrug resistance. Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients.
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PMID:Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporine. 197 61

Many cancers have been cured by chemotherapeutic agents. However, other cancers are intrinsically drug resistant, and some acquire resistance following chemotherapy. Cloning of the cDNA for the human MDR1 gene (also known as PGY1), which encodes the multidrug efflux protein P-glycoprotein, has made it possible to measure levels of MDR1 RNA in human cancers. We report the levels of MDR1 RNA in greater than 400 human cancers. MDR1 RNA levels were usually elevated in untreated, intrinsically drug-resistant tumors, including those derived from the colon, kidney, adrenal gland, liver, and pancreas, as well as in carcinoid tumors, chronic myelogenous leukemia in blast crisis, and cell lines of non-small cell carcinoma of the lung (NSCLC) with neuroendocrine properties. MDR1 RNA levels were occasionally elevated in other untreated cancers, including neuroblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma. MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma. Many types of drug-sensitive and drug-resistant tumors, including NSCLC and melanoma, contained undetectable or low levels of MDR1 RNA. The consistent association of MDR1 expression with several intrinsically resistant cancers and the increased expression of the MDR1 gene in certain cancers with acquired drug resistance indicate that the MDR1 gene contributes to multidrug resistance in many human cancers. Thus, evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents. The information may be useful in designing or altering chemotherapeutic protocols in these patients.
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PMID:Expression of a multidrug resistance gene in human cancers. 256 56

Anti-P-glycoprotein monoclonal antibody JSB-1 and alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunocytochemical staining technique were used to study the relation between P-glycoprotein expression and clinical multidrug resistance (MDR) in 42 patients with acute leukaemia (23 ALL and 19 ANLL). 10 of 17 patients who were diagnosed as refractory or relapsed acute leukaemia were positive with P-glycoprotein expression, while only 3 of 14 newly diagnosed and 1 of 11 who were in complete remission were positive. The preliminary results indicated that there was a close association between the P-glycoprotein expression and the clinical resistance to chemotherapy in some patients.
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PMID:[Detection of P-glycoprotein expression in patients with acute leukaemia and clinical significance]. 771 12

Bone marrow specimens from 100 cases of acute leukemia (AL) diagnosed by MIC were detected with fluorescence microscopy for their mdr-1 expression using monoclonal antibody JSB-1 against P-glycoprotein (P-170). The results showed that almost all subtypes of AL had P-170 expression and M5 of ANLL had a significantly higher expression rate in the newly diagnosed group. The MDR expression highly correlated with the clinical drug resistance and prognosis. The Positive rate of P-170 (20.8% +/- 14.9%) and MDR expression (78.9%) of refractory group were significantly higher than newly diagnosed group (7.5% +/- 9.8% and 18.2% respectively). Cases with MDR expression had poor response to chemotherapy and bad prognosis.
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PMID:[Detection and analysis of multidrug resistance in 100 cases of acute leukemia]. 789 88

To evaluate the clinical and biological significance of P-glycoprotein (P-gp) expression in adult acute nonlymphocytic leukemia (ANLL), P-gp was detected in 169 patients including 152 previously untreated cases, 7 refractory cases, and 10 cases at remission by using monoclonal antibody UIC2 and flow cytometry. P-gp was expressed in 29% of previously untreated cases, being less than in 71% of the refractory cases. P-gp expression was not found in patients at remission. Morphologically, P-gp expression was high in hybrid acute leukemia (67%) and acute monoblastic leukemia (47%) subtypes. Immunologically, P-gp expression was significantly associated with CD34, CD7, CD14 or CD42b/CD61. Cytogenetically, P-gp expression was highly associated with poor prognosis abnormalities (54%), which was significantly higher than 7% of P-gp expression in good prognosis abnormalities. 23% of P-gp positive previously untreated ANLL (not including M3) achieved complete remission; this was significantly lower than 76% in P-gp negative cases. These suggested that P-gp expression is an index of poor prognosis in adult ANLL and P-gp positive ANLL has unique clinical and biological features.
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PMID:[The clinical and biological significance of P-glycoprotein expression in acute nonlymphocytic leukemia]. 1037 70